Myricetin Possesses Potential Protective Effects on Diabetic Cardiomyopathy through Inhibiting I<i>κ</i>B<i>α</i>/NF<i>κ</i>B and Enhancing Nrf2/HO‐1

Abstract

Diabetic cardiomyopathy (DCM) is associated with a greater risk of mortality in patients with diabetes mellitus. Currently, no specific treatment has been suggested for DCM treatment. This study demonstrated that myricetin (M) attenuated DCM-associated cardiac injury in mice subjected to streptozotocin (SZT) and in neonatal rat cardiomyocytes (NRCM) challenged with high glucose. <i>In vivo</i> investigation demonstrated 6 months of M treatment (200 mg/kg/d) significantly alleviated cardiac hypertrophy, apoptosis, and interstitial fibrosis. Mechanically, M treatment significantly increased the activity of Nrf2/HO-1 pathway, strengthening antioxidative stress capacity evidenced by reversed activities of GPx and SOD, and decreased MDA production. M treatment also inhibited I<i>κ</i>B<i>α</i>/NF-<i>κ</i>B pathway, resulting in reduced secretion of inflammation cytokines including IL-1<i>β</i>, TNF-<i>α</i>, and IL-6. Besides, the TGF<i>β</i>/Smad3 signaling was also blunted in DCM mice treated with M. These beneficial effects of M treatment protected cardiomyocytes from apoptosis as shown by decreased TUNEL-positive nucleus, c-caspase 3, and Bax. Similar effects of M treatment could be reproduced in NRCM treated with high glucose. Furthermore, through silencing Nrf2 in NRCM, we found that the regulation of I<i>κ</i>B<i>α</i>/NF<i>κ</i>B by M was independent on its function on Nrf2. Thus, we concluded that M possesses potential protective effects on DCM through inhibiting I<i>κ</i>B<i>α</i>/NF<i>κ</i>B and enhancing Nrf2/HO-1.